Adapted Treatment of Epstein-Barr Virus Infection to Prevent Posttransplant Lymphoproliferative Disorder After Heart Transplantation

Up to 35% of posttransplant lymphoproliferative disorder (PTLD) cases occur within 1 year of transplantation, and over 50% are associated with Epstein-Barr virus (EBV). EBV primary infection and reactivation are PTLD predictive factors, but there is no consensus for their treatment. We conducted a prospective single-center study on 299 consecutive heart-transplant patients treated with the same immunosuppressive regimen and monitored by repetitive EBV viral-load measurements and endomyocardial biopsies to detect graft rejection. Immunosuppression was tapered on EBV reactivation with EBV viral loads >10(5)copies/mL or primary infection. In the absence of response at 1 month or a viral load >10(6)copies/mL, patients received one rituximab infusion (375mg/m(2)). All patients responded to treatment without increased graft rejection. One primary infection case developed a possible PTLD, which completely responded to diminution of immunosuppression, and one patient, whose EBV load was unevaluable, died of respiratory complications secondary to PTLD. Compared with a historical cohort of 820 patients, PTLD incidence was decreased (p=0.033) by a per-protocol analysis. This is the largest study on EBV primary infection/reactivation treatment, the first using rituximab following solid organ transplantation to prevent PTLD and the first to demonstrate an acceptable tolerability profile in this setting. The authors show that an algorithm assessing EpsteinBarr virus viral load, and responding with decreasing immunosuppression and rituximab, is highly effective in controlling posttransplant lymphoproliferative disorder in heart transplant patients.